Assessing Former Preterm Neonates for Iron Deficiency at Four Months of Age: Is Breastfeeding a Risk Factor?

2021 ◽  
Vol 104 (6) ◽  
pp. 998-1004

Objective: To determine the incidence and risk factors of iron deficiency (ID) among preterm infants when they reached four months postnatal age. Materials and Methods: The present study was a prospective cohort study. Infants born at 34 weeks’ gestation or earlier, weighing 2,000 grams or less, and treated at a university hospital in Bangkok, Thailand between January 2010 and June 2014 were enrolled. Study data collected included demographic and clinical information during hospitalization, breast milk or formula, and iron supplementation reported during follow-up visits, and studies of iron status at 4-months postnatal age. Univariate and multivariate analyses were performed to identify factors associated with ID. Results: One hundred twenty-one infants completed the four months follow-up. At hospital discharge, all infants were exclusively or partially breastfed. Prophylactic ferrous sulfate was prescribed in 110 infants. At 4-month, 65% were exclusively or partially breastfed. Incidence of biochemical ID or ID anemia in exclusively breastfed, partially breastfed, and formula-fed infant were 19%, 6.9%, and 4.8%, respectively. After adjusting for birth weight and prophylactic ferrous sulfate supplementation, breastfeeding was not associated with increased risk of ID or ID anemia. Conclusion: Incidence of ID at 4-month postnatal age of exclusively breastfed, partially breastfed, and formula-fed preterm infant were not statistically different. Prophylactic iron supplementation at 2 to 4 mg/kg/day should be prescribed to all exclusively or partially breastfed preterm infants of 34 weeks’ gestation or less to prevent ID. The authors recommend checking iron status at the 4-month postnatal time point regardless of feeding type. Trial registration: Thai Clinical Trials Registry, TCTR20201028002 Keywords: Breastfeeding; Cohort study; Infant iron status; Iron deficiency anemia; Iron supplements; Preterm infants

2021 ◽  
Author(s):  
Phakatip Sinlapamongkolkul ◽  
Pacharapan Surapolchai ◽  
Vip Viprakasit

Abstract Background Many clinicians hesitate adopting a universal infant iron supplementation program due to the risk of increased iron absorption for those with thalassemia. We aimed to determine thalassemia prevalence in 6- to 12-month old infants, along with the iron status of those with and without thalassemia. Procedures: We performed a cross-sectional descriptive study of infants attending the Well Baby Clinic at Thammasat University Hospital for routine checkups. Complete blood count, hemoglobin electrophoresis, iron parameters, and molecular genetics for common α- and β-thalassemia were evaluated. Results Overall, 97 of 206 (47%) participants had thalassemia minor, the majority having Hb E traits. None had thalassemia intermedia or major. Familial history of anemia or thalassemia presented an increased risk of detecting thalassemia minor in offspring (OR 5.18; 95% CI 2.60-10.33, p = 0.001). There were no statistical differences in transferrin saturation, serum ferritin and hepcidin between iron-replete infants with thalassemia minor and those without. However, one-third of infants with thalassemia minor (31/97) also had iron deficiency anemia (IDA), with a similar risk of having iron deficiency to infants without thalassemia. There was no hepcidin suppression in our infants with thalassemia minor as compared to controls. Conclusions Both thalassemia and IDA are endemic to Southeast Asia. Infants with thalassemia minor, particularly with Hb E and α-thalassemia traits, are at risk of IDA. Our short-term universal iron supplementation program for 6 to 12-month old infants does not appear to increase the risk of those with thalassemia minor developing iron overload in the future.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1737-1737
Author(s):  
Jordie Fischer ◽  
David Goldfarb ◽  
Rajavel Elango ◽  
Crystal Karakochuk

Abstract Objectives In 2016, the World Health Organization set a global policy recommending daily iron supplementation (60 mg elemental iron) for women living in countries with anemia prevalence >40%, such as in Cambodia (45%). However, recent studies have shown the prevalence of iron deficiency (ferritin < 15 μg/L) to be low in Cambodian women (∼3%). Further, iron supplementation may be harmful in women with genetic hemoglobin disorders, which are common in Cambodia (60%), as they are already at an increased risk of iron overload. Iron salts (e.g., ferrous sulfate) are the most common form of iron supplement but have poor bioavailability. Less than 20% of the iron is absorbed in the gut, and the remaining 80% passes unabsorbed into the colon, potentially increasing the risk of pathogen growth and gut inflammation. Alternatively, ferrous bisglycinate is a newer form of iron supplement that has 2–4x higher bioavailability than ferrous sulfate.   Our objectives are to assess in women of childbearing age in Cambodia: i) the non-inferiority of 18 mg iron as ferrous bisglycinate as compared to 60 mg iron as ferrous sulfate on mean ferritin concentrations; and ii) if ferrous sulfate administration is associated with increased intestinal inflammation and enteropathogen abundance, as compared to placebo or ferrous bisglycinate. Methods We will undertake a double-blind three-arm RCT in Kampong Thom province, Cambodia. We will recruit and randomize 480 non-pregnant women (18–45 years) to receive 60 mg ferrous sulfate, 18 mg ferrous bisglycinate, or placebo, for 12 weeks. We will collect blood and stool samples at baseline and 12 weeks, which will be used to measure hemoglobin and ferritin concentrations for iron status, fecal calprotectin, a marker of gut inflammation, and perform multiplex molecular enteropathogen testing. Results N/A Conclusions The findings of this trial will contribute to the evidence for safe and effective iron supplementation for women worldwide. Funding Sources Canadian Institutes of Health Research.


2021 ◽  
Vol 9 ◽  
Author(s):  
Mingyan Li ◽  
Ying Lv ◽  
Jionghuan Ying ◽  
Lin Xu ◽  
Weijun Chen ◽  
...  

Objective: The aim of this study was to investigate the effects of unified iron supplementation and identify the factors related to the iron homeostasis among preterm infants.Method: A total of 250 preterm infants were divided into neonatal anemic (NA, n = 154) and non-neonatal anemic group (NNA, n = 96). Iron supplements at a dose of 2 mg/kg per day were given from 40 weeks' gestational age to 6 months. Iron status parameters were measured at 3 and 6 months, respectively. Prevalence of iron deficiency (ID) and iron deficiency anemia (IDA), and the correlated factors were analyzed. Growth and side-effects were monitored.Results: There were no significant differences for the prevalence of ID or IDA between the two groups. Multivariate regression analyses showed that higher Hb at birth and early treatment of blood transfusion reduced the risk of ID/IDA at 3 months (all p < 0.05); while higher level of Hb at 3 months (p = 0.004) and formula feeding reduced the occurrence of ID/IDA at 6 months (p < 0.05); males had a 3.35 times higher risk to develop ID/IDA than girls (p = 0.021). No differences in growth and side effects were found.Conclusion: A daily dose of 2 mg/kg iron supplement is beneficial to maintain iron homeostasis in majority preterm infants within 6 months regardless of their neonatal anemia history. Under the routine iron supplementation, Hb level at birth and at 3 months, early treatment of blood transfusion, gender and feeding patterns are the major factors affecting the prevalence of ID/IDA among preterm infants in infancy.


2021 ◽  
Author(s):  
Rebecka Hansen ◽  
Anne Lærke Spangmose ◽  
Veronika Markova Sommer ◽  
Charlotte Holm ◽  
Finn Stener Jørgensen ◽  
...  

Abstract Purpose: To assess the following in singleton pregnant women: 1) associations between first trimester iron deficiency and obstetric and perinatal outcomes, 2) overall first trimester iron status and 3) post-treatment iron status after intensified iron supplementation.Methods: Prospective cohort study with linkage of first trimester hemoglobin and plasma ferritin with obstetric and perinatal data from a hospital database. Blood sample data were obtained at a Danish University Hospital. The cohort was divided into groups according to ferritin and hemoglobin: (1) iron deficient anemic (ferritin <30 ng/mL and Hb <110 g/L), (2) iron deficient non-anemic (ferritin <30 ng/mL and Hb ≥110 g/L), and (3) iron replete non-anemic (ferritin 30–200 ng/mL and Hb ≥110 g/L). Obstetric and perinatal outcomes in each iron deficient group were compared to the iron replete non-anemic group using multivariable logistic regression. The effect of 2–8 weeks intensified iron supplementation on hemoglobin and ferritin were assessed by pairwise comparisons.Results: The cohort comprised 5,763 singleton pregnant women, of which 14.2% had non-anemic iron deficiency, and 1.2% had iron deficiency anemia. Compared to iron replete non-anemic women, iron deficient anemic women had a higher risk of gestational diabetes (aOR 3.8, 95% CI 1.4–9.0), and iron deficient non-anemic women had a higher risk of stillbirth (aOR 4.0, 95% CI 1.0–14.3). In group 1 and 2, 78.7% and 67.8% remained iron deficient after intensified iron supplementation. Conclusion: First trimester iron deficiency may be associated with gestational diabetes and stillbirth. First trimester iron deficiency was present in 15.4% and often persisted despite 2–8 weeks intensified iron supplementation.


Author(s):  
Herng-Sheng Lee ◽  
Shih-Yu Lee ◽  
Wan-Ting Huang ◽  
Solomon Chih-Cheng Chen ◽  
Hsin-Yi Yang

IntroductionThis study evaluated the association between iron deficiency anemia (IDA) and migraine and investigated the effects of iron supplementation, and comorbid conditions, including cardiovascular, respiratory, hepatic, endocrine, metabolic, and other diseases on migraine development.Material and methodsAll study subjects aged ≥20 years with newly diagnosed IDA in the Taiwan National Health Insurance Database during 2000–2012 were enrolled. We matched IDA and non-IDA subjects according to age and sex at a 1:2 ratio. Our primary outcome was diagnosis of migraine, and the patients were monitored until the end of 2013. A Cox proportional hazards regression model was used to evaluate the risk of migraine events in IDA.ResultsThe cumulative incidence of migraine in patients with IDA was 5.82 per 1,000 person-years, which was higher than that in the comparison group (3.99 per 1,000 person-years) during the follow-up period (log-rank test, p < 0.001). After controlling for potentially confounding factors, the risk of migraine was higher in the IDA group compared with the non-IDA group (the adjusted hazard ratio = 1.68, 95% CI = 1.51−1.87, p < 0.001). Female and ≤50 year-old IDA patients with or without iron supplementation use had an increased incidence of migraine (p < 0.05).ConclusionsOur study provided additional evidence of an increased risk of migraine in patients with IDA. We also found that females and ≤50 year-old IDA patients with or without iron supplementation use had an increased risk of migraines.


2004 ◽  
Vol 74 (6) ◽  
pp. 435-443 ◽  
Author(s):  
Hertrampf ◽  
Olivares

Iron amino acid chelates, such as iron glycinate chelates, have been developed to be used as food fortificants and therapeutic agents in the prevention and treatment of iron deficiency anemia. Ferrous bis-glycine chelate (FeBC), ferric tris-glycine chelate, ferric glycinate, and ferrous bis-glycinate hydrochloride are available commercially. FeBC is the most studied and used form. Iron absorption from FeBC is affected by enhancers and inhibitors of iron absorption, but to a lesser extent than ferrous sulfate. Its absorption is regulated by iron stores. FeBC is better absorbed from milk, wheat, whole maize flour, and precooked corn flour than is ferrous sulfate. Supplementation trials have demonstrated that FeBC is efficacious in treating iron deficiency anemia. Consumption of FeBC-fortified liquid milk, dairy products, wheat rolls, and multi-nutrient beverages is associated with an improvement of iron status. The main limitations to the widespread use of FeBC in national fortification programs are the cost and the potential for promoting organoleptic changes in some food matrices. Additional research is required to establish the bioavailability of FeBC in different food matrices. Other amino acid chelates should also be evaluated. Finally there is an urgent need for more rigorous efficacy trials designed to define the relative merits of amino acid chelates when compared with bioavailable iron salts such as ferrous sulfate and ferrous fumarate and to determine appropriate fortification levels


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amanda Bries ◽  
Chong Wang ◽  
Brian Wels ◽  
Isaac Agbemafle ◽  
Olivia Meier ◽  
...  

Abstract Objectives Iron deficiency anemia (IDA) is a widespread nutritional deficiency. Iron supplementation with ferrous sulfate (FeSO4) is the most common strategy to treat IDA; however, the compliance with daily FeSO4 administration is poor, due to contraindicating side effects. Previously, we have reported that A. oryzae (Ultimine®; ULT) is a novel iron source. Therefore, the objective of this study was to determine the biochemical assessment, non-transferrin bound iron (NTBI) and commonly related gastrointestinal side effects to assess the safety of A. oryzae compared to FeSO4. Methods Female participants (n = 16) with serum ferritin concentrations 40 µg/L were randomized to a double-blind, 9-wk cross-over study with a 3-wk placebo washout period between treatments. Oral iron supplements (65 mg Fe), FeSO4 and ULT were administered for 21 consecutive days for each subject. Side effect questionnaires were collected 3d/wk over the 9-wk study period. Side effects and biochemical markers (nausea, heartburn, abdominal pain, fatigue, headache, diarrhea, constipation, oxidative stress and liver and kidney function) from iron supplementation were evaluated, along with serum iron, % transferrin saturation (TS) and NBTI 8 h curves. Results Serum iron, TS, and NTBI were all markedly higher with FeSO4 at each time-point from 2–8 hours (P < 0.001) compared to ULT, whereas NTBI was undetected. Among treatments, FeSO4 resulted in higher inflammation, though not statistically significant. Compliance based on returned pills was higher with ULT (97.3%) than placebo and FeSO4 (95.2% and 93.2%, respectively). Subjects taking FeSO4 reported abdominal discomfort 2% more than ULT, which was not significantly different. FeSO4 caused marginally higher incidence of combined nauseation, constipation and diarrhea when subjects were taking FeSO4 (P < 0.07). Iron status was maintained similarly by both oral iron supplements. Oxidative stress, inflammation, kidney and liver function markers were not elevated with ULT supplementation, suggesting safety of its consumption. Conclusions Better compliance and less gastrointestinal related side effects were reported with ULT compared to FeSO4, while maintaining normal iron status. Our data suggests ULT is a safe oral iron supplement for treatment of IDA. Funding Sources Cura Global Health, Inc.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Carmen Landry ◽  
Jon Dorling ◽  
Ketan Kulkarni ◽  
Marsha Campbell-Yeo ◽  
Michael Vincer ◽  
...  

Background: Iron is an essential micronutrient, especially in infants and young children and is required for erythropoiesis and development of the central nervous system. However, iron deficiency (ID) is the most common micronutrient deficiency worldwide. ID and iron deficiency anemia (IDA) have been associated with poor neurodevelopmental and behavioural outcomes later in life. Preterm infants are particularly at risk of developing ID in early life due to lower iron stores at birth, accelerated growth in the first weeks of life and multiple phlebotomies while in hospital. Therefore, international recommendations suggest prophylactic iron therapy of 2-4 mg/kg/day starting at 2-6 weeks of age until at least 6-12 months in preterm and low birth weight infants. This prophylactic iron supplementation has been shown to be effective at reducing the incidence of ID and IDA. However, the published work mainly involves moderate to late preterm infants and the research is lacking on iron status after discharge in very preterm infants (VPI, &lt;31 weeks gestational age). Based on our previous work, 32% of the VPIs were iron deficient at 4-6 months corrected age despite this early supplementation. Since the development of ID may have permanent detrimental effects on the developing brain of these high-risk preterm infants, a knowledge of risk factors for ID is also important to identify strategies focused on its prevention. Objective: To investigate the risk factors associated with development of ID Methods: A retrospective cohort study was conducted at the IWK Health Centre using a population based provincial Perinatal Follow-Up Program database. All live-born VPIs born in Nova Scotia between 2005-2018 were included. Patients with congenital malformations, chromosomal anomalies, or who died prior to outcome assessment were excluded. As a standard of care, all these infants were started on prophylactic iron supplements (2-3 mg/kg/day) at 2-4 weeks of chronological age. Iron dosage was regularly adjusted during the hospital stay as guided by serum ferritin levels. At discharge, it was recommended to continue iron prophylaxis until 9-12 months corrected age. All these infants underwent a blood test during their first neonatal follow-up visit at 4-6 months corrected age to check for hemoglobin, reticulocyte count and serum ferritin. ID was defined as serum ferritin &lt;20g/l or &lt;12g/l at 4 and 6 months respectively. A univariate analysis was performed by using a series of single variable logistic regression models to identify the factors associated with presence of ID. Factors with a p-value &lt; 0.20 in the univariate analysis were entered into a multivariable risk model for occurrence of ID using a backwards selection procedure. Variables with a p-value &lt; 0.05 were retained. Results: Of 411 infants included in the study, 32.1% (n=132) had ID. The prevalence of ID decreased over time (37.6% in 2005-2011 vs 25.8% in 2012-2018 cohort). Table 1 compares the antenatal and neonatal characteristics of the ID and non-ID groups. Table 2 compares sociodemographic variables and clinical variables at the time of follow up of the two groups. Independent risk factors for ID were: gestational age (&lt;27 weeks to &gt;27 weeks) (OR:1.7 (1.0-2.9), p=0.04) and gestational hypertension (OR: 2.1(1.2-3.7), p=0.009). Independent factors protective for ID were: mixed feeding (breast milk and formula compared to formula alone) (OR: 0.5 (0.2-0.9), p=0.021) and iron supplementation at follow-up (OR:0.5 (0.3-0.9), p=0.02). Conclusion(s): Despite prophylactic iron supplementation, one-third of VPIs had ID at 4-6 months corrected age. Gestational hypertension in mother and gestational age &lt; 27 weeks were independent risk factors for ID. In addition, despite adjusting for iron supplementation at follow-up, the formula feeding group was more likely to have ID compared to the mixed feeding group. This may be because of the sub-therapeutic iron intake in the formula fed infants. It is often thought that formula milk may have sufficient iron to meet the demands of growing infants and thus, they are less likely to receive higher doses of supplemental iron beyond what is contained in the formula. However, this may not be true since the iron present in formula may not have the same bioavailability as breast milk. Future prospective studies are required to further validate these observations. Nonetheless, the study identified important areas to mitigate ID in VPIs. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2052-2052
Author(s):  
Eldad A. Hod ◽  
Eric H. Ekland ◽  
Shruti Sharma ◽  
Boguslaw S. Wojczyk ◽  
David A. Fidock ◽  
...  

Abstract Abstract 2052 To clarify the interactions between iron status, oral iron supplementation, and bacterial and malarial infections, we examined iron-replete mice and mice with dietary iron deficiency infected with Salmonella typhimurium, Plasmodium yoelii, or both, with and without oral iron administration. These studies were designed to identify potential mechanisms underlying the increased risk of severe illness and death in children in a malaria-endemic region who received routine iron and folic acid supplementation during a randomized, controlled trial in Pemba, Tanzania (Sazawal et al. Lancet 2006;367:133-43). To this end, weanling C57BL/6 female mice were fed an iron-replete or an iron-deficient diet, the latter of which resulted in severe iron deficiency anemia. Groups of mice were then infected by intraperitoneal injection of Salmonella typhimurium strain LT2, Plasmodium yoelii strain 17X parasites, or both. With Salmonella infection alone, iron-deficient mice had a median survival (7.5 days, N=8) approximately half that of iron-replete mice (13 days, N=10, p<0.0001). At death, the mean level of bacteremia was significantly higher in infected iron-deficient mice. In blood cultures performed at death, all iron-deficient mice were bacteremic, but bacteria were detected in only 4 of 10 iron-replete mice. Both iron-deficient and iron-replete Salmonella-infected mice had gross hepatosplenomegaly with hepatitis, distorted hepatic and splenic architecture, massive expansion of the splenic red pulp with inflammatory cells, and Gram-negative bacilli by tissue Gram stain. With P. yoelii infection alone, iron-deficient and iron-replete mice cleared the infection at similar rates (by ~13 days following infection, N=5 in each group) and no deaths due to parasitemia occurred. With Salmonella and P. yoelii co-infection, death was earlier than with Salmonella alone in iron-replete mice (median survival of 10 vs. 13 days; N=10 in each group; p=0.005), but not in iron-deficient mice (median survival of 7 vs. 7.5 days; N=10 and 8, respectively; p=0.8). To examine the effect of short-term oral iron supplementation with Salmonella infection alone, mice received daily iron (ferrous sulfate, 1 mg/kg) by gavage for 4 days before infection with Salmonella, and supplementation continued for a total of 10 days. After gavage, plasma non-transferrin-bound iron (NTBI) appeared at 1–2 hours with a mean peak level of approximately 5 μM. In iron-deficient mice, short-term oral iron supplementation did not fully correct the iron deficiency anemia or replenish iron stores. Oral iron supplementation reduced the median survival of both iron-deficient and iron-replete Salmonella-infected mice by approximately 1 day; the difference was significant only in the iron-replete group (N=5, p<0.05). In summary, these results indicate that iron deficiency decreases the survival of Salmonella-infected mice; the median survival of iron-deficient mice was approximately half that of those that were iron replete. These observations are similar to those in the Pemba sub-study in which iron-deficient children given placebo had a 200% increase in the risk of adverse events relative to iron-replete children. Iron deficiency had no apparent effect on the course of infection with P. yoelii but further studies with more virulent Plasmodium species are needed. Co-infection with Salmonella and Plasmodium significantly increased mortality as compared to single infections, but only in iron-replete mice. Oral iron supplementation of Salmonella-infected mice significantly decreased the median survival, but only of iron-replete animals; however, our study may have had insufficient power to detect an effect on iron-deficient mice. Systematic examination in mice of the effect of iron supplements on the severity of malarial and bacterial infection in iron-replete and iron-deficient states may ultimately help guide the safe and effective use of iron interventions in humans in areas with endemic malaria. Disclosures: No relevant conflicts of interest to declare.


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